Alterations in Gut Microbiota and Metabolism in Cirrhotic Portal Hypertension: Implications for Disease Progression

Abstract

BackgroundAlthough gut microbiota has been implicated in various liver disorders, its relationship with cirrhotic portal hypertension (CPH) remains unclear.AimsTo investigate the structural and functional alterations of gut microbiota in patients with CPH and the potential role of these alterations in the progression of CPH.MethodsWe collected faecal samples from 35 patients with CPH and 71 patients without CPH (controls) to conduct microbiome and metabolomic analyses. Gut microbes, faecal metabolites and their functional pathways associated with CPH were identified using multiple bioinformatics approaches. To understand the role of gut microbiota in the pathogenesis of CPH, we carried out faecal microbiota transplantation, CPH‐characteristic bacterial transplantation and antibacterial experiments in mice.ResultsMicrobial diversity was diminished, and gut microbial structures were altered in patients with CPH compared to the controls, primarily manifested as increased abundance of lipopolysaccharide‐producing bacteria and decreased abundance of anti‐inflammatory bacteria. This dysbiosis of gut microbiota was accompanied by changes in the faecal metabolome, particularly in arginine biosynthesis and nitric oxide production. Transplantation of gut microbiota from CPH patients, as well as the transplantation of CPH‐associated bacteria Veillonella nakazawae, was found to exacerbate CPH progression in mice. Antibiotic treatment significantly alleviated the CPH progression induced by N‐dimethylnitrosamine in mice.ConclusionsOur study reveals that gut microbiota dysbiosis is implicated in CPH progression, potentially providing new avenues for microbiome‐based treatment for CPH.